International Journal of Chronic Obstructive Pulmonary Disease最新文献

{"title":"Red Cell Distribution Width Predicts Mortality in Critically Ill Patients with COPD and Atrial Fibrillation: A Retrospective Cohort Study.","authors":"Bo Xie, Hong Teng, Yu-Fei Zhou, Peng-Fei Li, Jing Wang, Xiao-Jiao Cui","doi":"10.2147/COPD.S611640","DOIUrl":"10.2147/COPD.S611640","url":null,"abstract":"<p><strong>Background: </strong>Critically ill patients with COPD and atrial fibrillation (AF) face a substantially poor prognosis. Given the established prognostic value of red cell distribution width (RDW) in each condition alone, we sought to systematically evaluate its utility for mortality prediction in this population.</p><p><strong>Methods: </strong>This retrospective cohort study utilized data from the MIMIC-IV database. Adult ICU patients with concurrent COPD and AF were enrolled. The association between baseline RDW (analyzed both as a continuous variable and in quartiles) and the primary outcome of in-hospital mortality was assessed using multivariable logistic regression, with extensive adjustment for demographics, severity of illness, comorbidities, and treatments. Secondary outcomes included ICU, 28-day, 90-day, and 1-year all-cause mortality.</p><p><strong>Results: </strong>Among 1,252 eligible patients, a significant graded association was observed between RDW and in-hospital mortality (P for trend < 0.001). After full adjustment, each standard deviation increase in RDW was associated with a 13% rise in the odds of in-hospital death (adjusted OR 1.13, 95% CI 1.05-1.21). Patients in the highest RDW quartile had a 2.53-fold increased risk (adjusted OR 2.53, 95% CI 1.36-4.73) compared to the lowest quartile. This robust association was consistently observed for all secondary outcomes, with the risk of ICU, 28-day, 90-day, and 1-year mortality also showing significant, graded increases across RDW quartiles in the fully adjusted models (all P for trend < 0.01). Furthermore, the association remained stable across all predefined subgroup analyses.</p><p><strong>Conclusion: </strong>In critically ill patients with COPD and AF, elevated baseline RDW at ICU admission is independently associated with increased short- and long-term mortality, with a graded risk increase across RDW quartiles. As a non-specific, routinely available hematologic parameter, RDW may serve as an adjunctive marker for risk stratification in this vulnerable population.</p>","PeriodicalId":48818,"journal":{"name":"International Journal of Chronic Obstructive Pulmonary Disease","volume":"21 ","pages":"611640"},"PeriodicalIF":4.1,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13500016/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interventions Evaluated to Improve Inhaler Adherence in Patients with Chronic Obstructive Pulmonary Disease: A Scoping Review.","authors":"Yuxin Zhu, Jing Chen, Shuyuan Li, Bo Liu, Min Huang, Liang Xue, Silin Zheng, Houqiang Huang","doi":"10.2147/COPD.S623486","DOIUrl":"10.2147/COPD.S623486","url":null,"abstract":"<p><strong>Background: </strong>Inhalation therapy is central for chronic obstructive pulmonary disease (COPD) management. However, poor inhaler adherence is associated with increased mortality, decreased quality of life, and increased costs. Existing interventions, particularly their design and delivery across urban and rural settings, have not been comprehensively mapped.</p><p><strong>Objective: </strong>To map the available interventions evaluated to improve inhaler adherence among patients with COPD and characterize their components, delivery approaches, reported outcomes, and variation across urban and rural settings.</p><p><strong>Methods: </strong>Following the Arksey and O'Malley framework, nine databases were searched from inception to March 22, 2026, including PubMed, Cochrane Library, Embase, Medline, Web of Science, CNKI, WanFang Data, CBM, and CQVIP. Two researchers independently screened the literature, extracted data, and synthesized findings.</p><p><strong>Results: </strong>The 24 included studies were from seven countries (19 randomized controlled trials, 2 quasi-experimental studies, 1 prospective cohort study, and 2 pre-post studies); 16 were published in Chinese and 8 in English. Six categories were identified according to the primary intervention component: education-focused (n=8), behaviour-focused (n=4), inhaler technique-focused (n=4), multicomponent (n=3), transitional care-focused (n=4), and reminder-focused interventions (n=1). Five studies used digital delivery, including videoconferencing, telemedicine, SMS, a gamified website, and a WeChat mini-program. Most studies reported improved inhaler adherence, while one found no statistically significant difference. Twenty-two studies were conducted in urban settings; only two Chinese studies targeted rural populations, both used transitional care with face-to-face education, telephone follow-up, and family involvement.</p><p><strong>Conclusion: </strong>The combined evidence suggests that interventions were diverse and predominantly in urban settings. Theory-informed design, ongoing follow-up, technique reassessment, digital support, and caregiver involvement were frequently identified across interventions reporting improved adherence. However, heterogeneity in intervention characteristics and adherence measures limited comparability, while evidence from rural populations remained scarce. Future research should consider longer follow-up and digital technologies to deliver personalized, sustainable interventions, particularly in rural settings.</p>","PeriodicalId":48818,"journal":{"name":"International Journal of Chronic Obstructive Pulmonary Disease","volume":"21 ","pages":"623486"},"PeriodicalIF":4.1,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13499992/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148809243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predictive Value of Biological Age for All-Cause Mortality in Patients with COPD.","authors":"Wei Cheng, Yanqun Hou, Aiyuan Zhou, Cong Liu, Shuwan Huang, Yiyang Zhao, Ji Li, Zhili Deng, Tongtong Zhang, Rui Mao, Yan Tang, Pinhua Pan","doi":"10.2147/COPD.S617907","DOIUrl":"10.2147/COPD.S617907","url":null,"abstract":"<p><strong>Purpose: </strong>Although biological age has emerged as a robust predictor of mortality across multiple chronic diseases, its prognostic value in patients with COPD remains insufficiently defined. This study aimed to compare the predictive performance of major biological age biomarkers and to develop a mortality risk prediction model for COPD based on the optimal biomarker.</p><p><strong>Patients and methods: </strong>We included 19,882 patients with COPD who had complete survival data extending beyond 10 years, recruited between 2006 and 2010 from a large biobank cohort. Biological aging was quantified using phenotypic age (PhenoAge) and Klemera-Doubal Method biological age (KDM-BA). Time-dependent ROC analyses were performed to compare the discriminatory ability of these biomarkers for predicting all-cause mortality. Cox regression was subsequently developed to construct mortality prediction models, with time-dependent ROC, net reclassification index (NRI) and integrated discrimination improvement (IDI) analyses evaluating model performance. Decision curve analysis(DCA) was then performed to evaluate the clinical benefit of each model.</p><p><strong>Results: </strong>Among 19,882 patients with COPD, the mean chronological age was 59.9 ± 7.1 years, with a mean PhenoAge of 53.4 ± 9.4 years and a mean KDM-BA of 58.9 ± 12.8 years. Time-dependent ROC analyses showed that PhenoAge consistently outperformed chronological age, PhenoAge acceleration, and KDM-BA in predicting all-cause mortality at 5-, 10-, and 15-year follow-up. Based on univariate analyses and assessment of collinearity among pulmonary function variables, two Cox models were constructed. Models incorporating PhenoAge demonstrated higher AUCs, as well as positive NRI and IDI values, compared with chronological age-based models. DCA curves further indicated that PhenoAge-derived models provided greater net clinical benefit across most threshold probabilities.</p><p><strong>Conclusion: </strong>PhenoAge outperformed chronological age and KDM-BA in predicting all-cause mortality in COPD. PhenoAge-based models provided modest but consistent improvements in risk prediction over models based on chronological age and may complement individualized risk stratification.</p>","PeriodicalId":48818,"journal":{"name":"International Journal of Chronic Obstructive Pulmonary Disease","volume":"21 ","pages":"617907"},"PeriodicalIF":4.1,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13500022/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Current Status, Challenges, and Optimization Strategies for Self-Management in Patients with COPD: A Review.","authors":"Xing Zhang, Yefei Ruan, Lin Qiu","doi":"10.2147/COPD.S619864","DOIUrl":"10.2147/COPD.S619864","url":null,"abstract":"<p><p>This article aims to review the current status, challenges, and optimization strategies of self-management in patients with Chronic Obstructive Pulmonary Disease (COPD). As a core component of comprehensive COPD treatment, self-management plays a key role in controlling symptoms, preventing acute exacerbations, improving quality of life, and reducing the healthcare burden. This narrative review comprehensively outlines the core definitions, current implementation models, key influencing factors, and evaluation systems of self-management, and provides an in-depth analysis of the current bottlenecks in patient adherence, knowledge and skill acquisition, psychosocial support, and integration of medical resources. Based on these findings, this article proposes the integration of behavioral change theory, digital health technologies (such as mobile applications, remote monitoring), home monitoring and early warning systems, and minimal resource rehabilitation interventions as strategic approaches to overcome these barriers. This review concludes that building a personalized, technology-enabled, and sustainable support system is crucial for improving the effectiveness of COPD self-management and reducing the healthcare burden.</p>","PeriodicalId":48818,"journal":{"name":"International Journal of Chronic Obstructive Pulmonary Disease","volume":"21 ","pages":"619864"},"PeriodicalIF":4.1,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13499544/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148800265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Explainable Machine Learning for Predicting Deep Vein Thrombosis in Critically Ill Patients with COPD: Development and Multicenter External Validation.","authors":"Guangdong Wang, Tingting Liu, Wenwen Ji, Tingting Li, Zhuoyang Wang, Tinghua Hu, Xiaojian Wang, Zhihong Shi","doi":"10.2147/COPD.S609203","DOIUrl":"10.2147/COPD.S609203","url":null,"abstract":"<p><strong>Background: </strong>Deep vein thrombosis (DVT) is a frequent yet underrecognized complication in critically ill patients with chronic obstructive pulmonary disease (COPD). Existing risk assessment tools are not specifically tailored to this high-risk population. We aimed to develop and externally validate an interpretable machine-learning model for early prediction of DVT in ICU-admitted COPD patients.</p><p><strong>Methods: </strong>Adult COPD patients admitted to the ICU were identified from the MIMIC-IV database and randomly divided into training and internal validation cohorts. Eight machine-learning algorithms were constructed and compared. The best-performing model was externally validated in MIMIC-III and eICU cohorts. Model discrimination, calibration, and clinical utility were assessed using AUC, calibration plots, decision-curve analysis (DCA), and Brier scores. SHAP analysis was applied for global and individual interpretability. A web-based calculator was developed for clinical application.</p><p><strong>Results: </strong>Among 6,672 ICU patients with COPD, 462 (6.9%) developed DVT. XGBoost showed the best overall performance, with an AUC of 0.840 (95% CI 0.812-0.868) in the internal validation cohort and good calibration. External validation confirmed stable discrimination in both MIMIC-III and eICU cohorts. Model interpretation identified prolonged PTT, elevated RDW, reduced SpO₂, and increased respiratory rate as important contributors to DVT risk. Decision-curve analysis suggested potential clinical benefit across relevant risk thresholds.</p><p><strong>Conclusion: </strong>We developed and externally validated an explainable machine-learning model for early prediction of DVT in ICU patients with COPD. By providing individualized risk estimates and interpretable explanations, this tool may help clinicians identify high-risk patients earlier and support more targeted thromboprophylaxis and imaging surveillance strategies.</p>","PeriodicalId":48818,"journal":{"name":"International Journal of Chronic Obstructive Pulmonary Disease","volume":"21 ","pages":"609203"},"PeriodicalIF":4.1,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13499541/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148800303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Continuity of Care and Risks of Hospitalization and Mortality in COPD: A Nationwide Cohort Study.","authors":"Jisu Ko, Jae Hyeok Lim, Dan Bi Kim, Eun-Cheol Park","doi":"10.2147/COPD.S591959","DOIUrl":"10.2147/COPD.S591959","url":null,"abstract":"<p><strong>Purpose: </strong>Chronic obstructive pulmonary disease (COPD) is characterized by unpredictable patterns of exacerbations, making continuity of care (CoC) a critical component in disease management. CoC influences COPD exacerbation-related hospitalization and mortality. Therefore, we assessed the impact of CoC levels on subsequent hospital admissions and all-cause mortality among individuals with COPD.</p><p><strong>Patients and methods: </strong>This retrospective nationwide cohort study utilized National Health Insurance Service-Senior cohort data (2002-2019) and included 29,316 patients newly diagnosed with COPD. The primary exposure was longitudinal CoC level categorized as low (<0.7) or high (≥0.7). Alternative continuity indices (usual care provider, sequential continuity, and modified continuity indices) were also evaluated. Outcomes were COPD exacerbation-related hospitalization and all-cause mortality within 1 year of diagnosis. Cox proportional hazards models estimated hazard ratios (HRs), Kaplan-Meier curves, and cumulative incidence rates were used to assess outcomes, and the Log rank test was used for between-group comparisons.</p><p><strong>Results: </strong>Low CoC level were associated with an increased risk of 3-year COPD exacerbation-related hospitalization (HR 1.63, 95% CI 1.45-1.83) and all-cause mortality (HR 1.25, 95% CI 1.11-1.40) compared with high CoC level. Intermediate (0.4-0.7) and low (<0.4) CoC level showed progressively increased hospitalizations (HR 1.61, 95% CI 1.40-1.86 vs HR 1.65, 95% CI 1.38-1.97), and mortality (HR 1.24, 95% CI 1.07-1.43 vs HR 1.26, 95% CI 1.05-1.51), respectively. These findings remained consistent across alternative continuity indices. Low CoC level were associated with an increased risk of emergency (HR 1.48, 95% CI 1.19-1.83) and general hospital admissions (HR 1.70, 95% CI 1.47-1.95).</p><p><strong>Conclusion: </strong>Lower CoC scores level consistently associated with higher risks of COPD hospitalization and all-cause mortality across multiple continuity indices. Subgroup and sensitivity analyses indicated that fragmented outpatient care increased adverse outcomes. Strengthening longitudinal patient-provider relationships may reduce preventable hospitalizations and premature deaths in patients with COPD.</p>","PeriodicalId":48818,"journal":{"name":"International Journal of Chronic Obstructive Pulmonary Disease","volume":"21 ","pages":"591959"},"PeriodicalIF":4.1,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13499550/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148800242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Irisin, BMI, and SII as Predictors of Frequent Acute Exacerbations in COPD: Development of a Predictive Nomogram.","authors":"Zina Bai, Tongxinwei Sun, Wenhui Song, Zhiwei Zhang, Jing Li, Siyu Wu, Zheng Wang, Aihong Meng","doi":"10.2147/COPD.S617958","DOIUrl":"10.2147/COPD.S617958","url":null,"abstract":"<p><strong>Objective: </strong>Frequent acute exacerbations of chronic obstructive pulmonary disease (COPD) are associated with poor prognosis, but objective and easily applicable predictors remain limited. This study aimed to investigate the association of Irisin, body mass index (BMI), and systemic immune-inflammation index (SII) with frequent acute exacerbations in COPD and to develop a predictive nomogram.</p><p><strong>Methods: </strong>This single-center retrospective-prospective observational study included 96 patients hospitalized with acute exacerbation of COPD (AECOPD) between March 2023 and March 2025. Frequent exacerbation was defined as ≥2 acute exacerbations or ≥1 hospitalization for AECOPD within one year. Patients were classified into the frequent exacerbation group (n=34) and non-frequent exacerbation group (n=62). Clinical data and serum Irisin levels were collected. Group comparisons, correlation analysis, univariate and multivariable logistic regression analyses were performed, and a nomogram was developed. Model performance was evaluated using receiver operating characteristic (ROC) analysis, calibration curve, bootstrap internal validation, and decision curve analysis.</p><p><strong>Results: </strong>Compared with the non-frequent exacerbation group, the frequent exacerbation group had lower Irisin and BMI levels and higher white blood cell count, neutrophil count, and SII. Multivariable logistic regression showed that Irisin (OR=0.981, 95% CI: 0.974-0.989) and BMI (OR=0.980, 95% CI: 0.963-0.998) were independently associated with a lower risk of frequent exacerbations, whereas lnSII (OR=1.117, 95% CI: 1.012-1.234) was associated with a higher risk. The combined model yielded an area under the ROC curve of 0.856 (95% CI: 0.780-0.933), showing better discrimination than Irisin alone. Calibration and decision curve analyses suggested favorable internal performance.</p><p><strong>Conclusion: </strong>Irisin, BMI, and SII were associated with frequent acute exacerbations in COPD. The combined nomogram may provide a preliminary reference for risk stratification, but external validation is required before clinical application.</p>","PeriodicalId":48818,"journal":{"name":"International Journal of Chronic Obstructive Pulmonary Disease","volume":"21 ","pages":"617958"},"PeriodicalIF":4.1,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13496126/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148800332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Questionnaire-Based Assessment of Physical Disability in COPD.","authors":"Joffroy Rogier, Alexandre Vivien, Loïs Bolko, Sandra Dury, Jean-Hugues Salmon, Valérian Dormoy, Julien Ancel, Gaëtan Deslee, Jeanne-Marie Perotin","doi":"10.2147/COPD.S615741","DOIUrl":"10.2147/COPD.S615741","url":null,"abstract":"<p><strong>Purpose: </strong>Chronic Obstructive Pulmonary Disease (COPD) is characterized by a progressive limitation of exercise capacity and functional disability, induced by both airway obstruction, skeletal muscle dysfunction and comorbidities, contributing to the disease burden. The Health Assessment Questionnaire - Disability Index (HAQ-DI), a validated tool assessing functional disability in rheumatologic diseases, with higher scores reflecting more severe disability, may be of interest in COPD. This study aimed to assess functional disability in COPD using the HAQ-DI and its association with disease severity and burden.</p><p><strong>Patients and methods: </strong>Mild to very severe COPD patients were included in the RINNOPARI prospective cohort (NCT02924818). Pulmonary function tests and 6-minute walking test (6MWT) results, HRCT emphysema quantification, and patient-reported outcomes, including mMRC, CAT, SGRQ, EQ-5D and SF-36, were recorded. Functional disability was assessed using the French version of the HAQ-DI.</p><p><strong>Results: </strong>A total of 117 patients were included, with a median HAQ-DI score of 0.38 [0.0-0.75]. HAQ-DI scores were significantly higher in COPD GOLD 3-4 (0.50 [0.13-0.75] vs 0.25 [0-0.63] in COPD GOLD 1-2, p = 0.015). HAQ-DI was associated with cardiovascular and depression comorbidities (p < 0.05), COPD clinical features (number of exacerbations, p = 0.015; mMRC dyspnea score, CAT score and 6MWT distance, all p < 0.001), and COPD burden as assessed by SF-36, SGRQ and HAD anxiety and depression scores, p < 0.001 for all. Multivariate analysis identified the 6MWT distance, CAT, SGRQ, and HAD-Depression scores as independent factors associated with HAQ-DI. We further identified a « High Functional Disability » (HFD) phenotype defined by HAQ-DI ≥ 1 (n = 20), and characterized by COPD poor prognosis markers and severe disease burden.</p><p><strong>Conclusion: </strong>The HAQ-DI is a feasible tool for screening functional disability in COPD. It allowed the identification of a « high-risk, high burden » phenotype, which could benefit from personalised management such as pulmonary rehabilitation and psychological support.</p>","PeriodicalId":48818,"journal":{"name":"International Journal of Chronic Obstructive Pulmonary Disease","volume":"21 ","pages":"615741"},"PeriodicalIF":4.1,"publicationDate":"2026-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13488665/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148800267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nuclear Factor Erythroid 2-Related Factor 2 in Chronic Obstructive Pulmonary Disease Progression: Regulation of Macrophage Polarization and Hyaluronic Acid Metabolism.","authors":"Ge Bai, Jiaqi Wang, Qianmei Wen, Yuning Huang, Haiqing Li, Yanhui Xu, Yiyi Liu, Erkang Yi, Fan Wu, Jieda Cui, Xinyue Mei, Yuxia Zhang, Yumin Zhou, Ruiting Sun, Pixin Ran","doi":"10.2147/COPD.S608922","DOIUrl":"https://doi.org/10.2147/COPD.S608922","url":null,"abstract":"<p><strong>Background: </strong>Alveolar microenvironment-driven macrophage polarization critically influences chronic obstructive pulmonary disease (COPD) progression. Nuclear factor erythroid 2-related factor 2 (NRF2), a key transcription factor, regulates macrophage polarization, suppresses inflammation, and promotes cellular repair. However, its role in macrophage-mediated inflammation and metabolic regulation, particularly hyaluronic acid (HA)-related remodeling, remains incompletely defined. This study investigates a novel dimension of NRF2 in COPD pathogenesis through macrophage-specific modulation, aiming to uncover its previously unrecognized mechanism.</p><p><strong>Methods: </strong>Macrophage-specific <i>Nrf2</i> knockout (KO) and control mice were chronically exposed to cigarette smoke (CS) to induce COPD-like pathology. Lung function, alveolar damage, macrophage polarization (M1/M2), and inflammatory cytokines were analyzed by respiratory function tests, histology, immunohistochemistry, and chemokine profiling, respectively. Proteomics approaches were used to identify dysregulated pathways.</p><p><strong>Results: </strong><i>Nrf2</i> KO mice displayed aggravated CS-induced lung dysfunction and alveolar destruction compared with control mice, accompanied by heightened M1 polarization and elevated pro-inflammatory cytokines (C-C motif chemokine ligand [CCL]2, CCL7, CXCL16). Proteomics revealed dysregulation of immune, oxidative stress, and metabolic pathways in the lungs of KO mice, including HA metabolism/uptake-associated proteins and increased CD44/CD74 expression. These findings suggest an association between NRF2 deficiency, macrophage polarization imbalance, and HA-related remodeling.</p><p><strong>Conclusion: </strong>Macrophage-specific NRF2 protects against CS-induced COPD-like lung injury by restraining inflammatory activation and preserving macrophage polarization-associated balance. Proteomic and validation analyses further nominate HA metabolism-related remodeling, particularly the CD44/CD74-associated response, as a biologically plausible feature of NRF2-deficient disease progression. These findings define a macrophage NRF2-linked inflammatory-remodeling axis in COPD-like pathology while highlighting the need for functional studies to establish whether HA/CD44 signaling is a causal downstream mechanism.</p>","PeriodicalId":48818,"journal":{"name":"International Journal of Chronic Obstructive Pulmonary Disease","volume":"21 ","pages":"608922"},"PeriodicalIF":4.1,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13484630/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148800301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exacerbations and Healthcare Burden of COPD with Type 2 Inflammation: US Claims Analysis.","authors":"Dharani K Narendra, Rosirene Paczkowski, Jihye Park, George Mu, Stefanie Kolterer, Emmeline Burrows, Stephen G Noorduyn, Shibing Yang","doi":"10.2147/COPD.S595066","DOIUrl":"https://doi.org/10.2147/COPD.S595066","url":null,"abstract":"<p><strong>Background: </strong>Up to 40% of patients with chronic obstructive pulmonary disease (COPD) have type 2 inflammation, characterized by an elevated blood eosinophil count (BEC), with limited real-world evidence of disease burden.</p><p><strong>Methods: </strong>Retrospective analysis using Optum's Clinformatics^® Data Mart Database, covering over 28 million lives of de-identified medical and pharmacy claims data in the US (commercial insurance and Medicare Advantage). Eligible patients required ≥2 COPD diagnosis claims (≥30 days apart) from January 2021 to December 2023, ≥40 years old at index date (last COPD diagnosis claim), continuous insurance coverage for ≥12 months both before (baseline) and after (follow-up) index date, triple therapy for ≥1 day and eligible BEC (≥14 days since last systemic corticosteroid use, if applicable) at baseline. Patients were categorized into three groups: with ≥2 moderate or ≥1 severe exacerbations (EXAC) and BEC ≥150 or ≥300 cells/µL at baseline (\"EXAC-EP-150\" and \"EXAC-EP-300\", respectively), and a reference group (BEC ≥150 cells/µL but not EXAC). Outcomes included COPD-related exacerbations, healthcare resource utilization (HCRU) and medical costs.</p><p><strong>Results: </strong>There were 13,840 eligible patients (6,389 EXAC-EP-150; 3,100 EXAC-EP-300; 7,451 reference). During 12-month follow-up, the mean (95% confidence interval) rates of any COPD-related exacerbations were similar in the EXAC-EP-150 and EXAC-EP-300 groups, both higher versus the reference group (1.58 [1.53, 1.63] and 1.56 [1.50, 1.63] vs 0.52 [0.50, 0.54]). Similarly, COPD-related HCRU and medical costs were higher in the EXAC-EP-150/300 groups than the reference group.</p><p><strong>Conclusion: </strong>Patients with COPD and type 2 inflammation experiencing exacerbations despite triple therapy have high exacerbation rates, HCRU, and medical costs, highlighting the need for improved management of this patient population.</p>","PeriodicalId":48818,"journal":{"name":"International Journal of Chronic Obstructive Pulmonary Disease","volume":"21 ","pages":"595066"},"PeriodicalIF":4.1,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13480161/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148800328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}